Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract
Open Access
- 16 April 2013
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
- Vol. 2, e00288
- https://doi.org/10.7554/elife.00288
Abstract
Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium.Keywords
Funding Information
- National Institutes of Health (P01 AI030731)
- National Institutes of Health (R37 AI042528)
- National Institutes of Health (K24 AI07113)
- National Institutes of Health (K23 AI087206)
- National Institutes of Health (K23 AI079394)
- National Institutes of Health (K23 AI071257)
- National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR000423)
- National Institutes of Health (P01 AI030731)
- National Institutes of Health (R37 AI042528)
- National Institutes of Health (K24 AI07113)
- National Institutes of Health (K23 AI087206)
- National Institutes of Health (K23 AI079394)
- National Institutes of Health (K23 AI071257)
- National Center for Advancing Translational Sciences (UL1TR000423)
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